The microstructure and mechanical properties of extruded Mg-Zn alloy containing Y element were investigated in temperature range of 300-450°C and strain rate range of 0.001-1 s-1 through hot compression tests.Pro...The microstructure and mechanical properties of extruded Mg-Zn alloy containing Y element were investigated in temperature range of 300-450°C and strain rate range of 0.001-1 s-1 through hot compression tests.Processing maps were used to indicate optimum conditions and instability zones for hot deformation of alloys.For Mg-Zn and Mg-Zn-Y alloys,peak stress,temperature and strain rate were related by hyperbolic sine function,and activation energies were obtained to be 177 and 236 kJ/mol,respectively.Flow curves showed that the addition of Y element led to increase in peak stress and decrease in peak strain,and indicated that DRX started at lower strains in Mg-Zn-Y alloy than in Mg-Zn alloy.The stability domains of Mg-Zn-Y alloy were indicated in two domains as 1)300°C,0.001 s-1;350°C,0.01-0.1 s-1 and 400°C,0.01 s-1 and 2)450°C,0.01-0.1 s-1.Microstructural observations showed that DRX was the main restoration mechanism for alloys,and fully dynamic recrystallization of Mg-Zn-Y alloy was observed at 450°C.The instability domain in Mg-Zn-Y alloy was located significantly at high strain rates.In addition,the instability zone width of Mg-Zn and Mg-Zn-Y alloys increased with increasing strain,and cracks,twins and severe deformation were considered in these regions.展开更多
This study was aimed at identifying underlying strengthening mechanisms and predicting the yield strength of as-extruded Mg-Zn-Y alloys with varying amounts of yttrium （Y） element. The addition of Y resulted in the ...This study was aimed at identifying underlying strengthening mechanisms and predicting the yield strength of as-extruded Mg-Zn-Y alloys with varying amounts of yttrium （Y） element. The addition of Y resulted in the formation of ternary 1 （Mg3YZn6）, W （Mg3Y2Zn3） and LPSO （Mg12YZn） phases which subse- quently reinforced alloys ZM31 ＋ 0.3Y, ZM31 ＋ 3.2Y and ZM31 ＋ 6Y, where the value denoted the amount of Y element （in wt%）. Yield strength of the alloys was determined via uniaxial compression testing, and grain size and second-phase particles were characterized using OM and SEM. In-situ high-temperature XRD was performed to determine the coefficient of thermal expansion （CTE）, which was derived to be 1.38 x 10^-5 K^-1 and 2.35 x 10^-5 K^-1 for W and LPSO phases, respectively. The individual strengthening effects in each material were quantified for the first time, including grain refinement, Orowan looping, thermal mismatch, dislocation density, load-bearing, and particle shearing contributions. Grain refinement was one of the major strengthening mechanisms and it was present in all the alloys studied, irrespective of the second-phase particles. Orowan looping and crE mismatch were the predominant strengthening mechanisms in the ZM31＋0.3Y and ZM31 ＋ 3.2Y alloys containing I and W phases, respectively, while load-bearing and second-phase shearing were the salient mechanisms contributing largely to the superior yield strength of the LPSO-reinforced ZM31 ＋ 6Y alloy.2017 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science ＆ Technology.展开更多
The particles of Mg-Zn-Gd icosahedral quasicrystal master alloy were added into the AZ31 alloy by the repeated plastic working(RPW)process in order to improve the mechanical properties of the AZ31 alloy at room temper...The particles of Mg-Zn-Gd icosahedral quasicrystal master alloy were added into the AZ31 alloy by the repeated plastic working(RPW)process in order to improve the mechanical properties of the AZ31 alloy at room temperature.The microstructure and tensile properties of composites were investigated by scanning electron microscopy(SEM),transmission electron microscopy(TEM),X-ray diffraction(XRD),and tensile testing machine at room temperature.The results suggest that the RPW process can effectively refine the matrix and make the I-phase particles distribute uniformly.The ultimate tensile strength and the yield strength of the composites reach their maximum values of 362.3 and 330.5 MPa,respectively,when the amount of I-phase particles added is10 %.Meanwhile,the elongation of the composites decreases sharply.展开更多
Through investigating and comparing microstructure and crystallographic texture of as-extruded Mg-14Li and Mg-14Li-6Zn-1Y(in wt%)alloys,the differences in their mechanical anisotropy were investigated.It revealed that...Through investigating and comparing microstructure and crystallographic texture of as-extruded Mg-14Li and Mg-14Li-6Zn-1Y(in wt%)alloys,the differences in their mechanical anisotropy were investigated.It revealed that the formation of I-phase(Mg3Zn6Y,icosahedral structure)can effectively refine grain size.Moreover,compared with Mg-14Li alloy,the texture type of Mg-14Li-6Zn-1Y alloy changed slightly,but its texture intensity decreased remarkably.As a result,the stronger texture contributed to the"normal"mechanical anisotropy of Mg-14Li alloy with higher tensile strength and a lower elongation ratio along transverse direction(TD)than those along extrusion direction(ED).However,for Mg-14Li-6Zn-1Y alloy,the zonal distribution of I-phase particles along ED caused"abnormal"mechanical anisotropy,i.e.higher tensile strength and better plasticity along ED.展开更多
Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in com...Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.展开更多
Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Ho...Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.展开更多
The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials. Early clinical trials are no exception, wit...The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials. Early clinical trials are no exception, with efforts to improve the eventual success rate of late stage trials through evolving phase I trial methodologies, the addition of extensive pharmacodynamic studies, and early adoption of patient selection strategies. Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges.展开更多
Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samp...Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.展开更多
An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were dis...An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were distributed evenly, and the particle size ranged from 20 to 260 nm（ average size ： 67.5 nm ）. Soybean lecithin played an important role in the emulsion system due to its abilities of acting as both absorption enhancer for insulin uptake through sublingual mucosa and oily phase for the emulsion system. The laser confocal scanning microscopic（LCSM） study showed that FITC-labelled insulin could penetrate the sublingual mucosa of rabbits, and the phase diagrams of the emulsion system suggested that soybean lecithin could take the place of oily phase to construct a stable emulsion system even if the traditional oil was absent. The applications of soybean lecithin as pharmaceutical biomaterial were extended for the further usage by present studies.展开更多
Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤...Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.展开更多
Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advan...Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.展开更多
Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cyto...Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cytopathology of Nipple Aspirate Fluid (NAF) has been shown to be an important adjunct to the currently accepted standard of medical care, i.e. mammography, coupled with physical examination, for the diagnosis of breast cancer. This is especially important for the subset of women aged 18-50 who are not identified as “high risk”, and therefore, for whom mammography is not routinely recommended. The objective of this study was to determine if a new, patented Class II medical device, the Mammary Aspirate Specimen Cytology Test (MASCT) System, designed to collect NAF for subsequent cytological examination is safe and effective. Methods: The MASCT medical device is a modified breast pump and was used to obtain bilateral specimens from 34 healthy, non-pregnant, female subjects for cytopathological examination. A conventional breast disease work-up was performed (medical history/risk factor collection, clinical breast examination and mammogram) and NAF specimens collected. Specimen weight was measured and a cytopathological examination was performed. Vital signs measurements, clinical laboratory analysis, and adverse event reporting were performed. Results: Based on cytopathological evaluation and/or measurable weight changes on the specimen collection membrane filter, all breasts evaluated (100%) yielded nipple aspirate fluid. Specimen weights ranged from <1 to 37 mg and all specimens evaluated cytopathologically were deemed to be clinically useful. One patient’s specimen was not available for cytopathological examination due to specimen mishandling, resulting in 60 breasts (representing 30 subjects) being evaluated cytologically. Fifty-eight of sixty breasts evaluated cytopathologically (97%) were reported as cytology Class I, and 2 of 60 (3%) were reported as cytology Class IIa. Cytopathological findings correlated well with mammogram and clinical breast exam results. No adverse events, including pain from the collection procedure, were reported. Conclusion: Based on this clinical study, we conclude that the Mammary Aspiration Specimen Cytology Test device is safe and effective for the collection of mammary aspirate specimens for laboratory cytopatho-logical testing.展开更多
The precondition of realizing feedback controlling DC DC converter to avoid chaotic state is to judge the behavior of the converter and take corresponding measures. In this paper, the output signals under different ci...The precondition of realizing feedback controlling DC DC converter to avoid chaotic state is to judge the behavior of the converter and take corresponding measures. In this paper, the output signals under different circuit parameters of the PWM buck converter have been analyzed. The method of using Fourier descriptor to extract output signals characteristics is put forward and proved to be a gist of identifying and classifying the behavior of DC DC converter. This method can establish a good foundation fo...展开更多
The noncollinear optical parametric amplification in BBO crystal is theoretically investigated. The phase matching angle, gain bandwidth, optimal noncollinear angle and conversion efficiency for both type-I and type-I...The noncollinear optical parametric amplification in BBO crystal is theoretically investigated. The phase matching angle, gain bandwidth, optimal noncollinear angle and conversion efficiency for both type-I and type-II BBO are simulated. The numerical simulation results are important to the practical optical parametric amplification experiments with BBO crystal.展开更多
Our aim in this paper is to study on the Caginalp for a conserved phase-field with a polynomial potentiel of order 2<em>p</em> - 1. In this part, one treats the conservative version of the problem of gener...Our aim in this paper is to study on the Caginalp for a conserved phase-field with a polynomial potentiel of order 2<em>p</em> - 1. In this part, one treats the conservative version of the problem of generalized phase field. We consider a regular potential, more precisely a polynomial term of the order 2<em>p</em> - 1 with edge conditions of Dirichlet type. Existence and uniqueness are analyzed. More precisely, we precisely, we prove the existence and uniqueness of solutions.展开更多
文摘The microstructure and mechanical properties of extruded Mg-Zn alloy containing Y element were investigated in temperature range of 300-450°C and strain rate range of 0.001-1 s-1 through hot compression tests.Processing maps were used to indicate optimum conditions and instability zones for hot deformation of alloys.For Mg-Zn and Mg-Zn-Y alloys,peak stress,temperature and strain rate were related by hyperbolic sine function,and activation energies were obtained to be 177 and 236 kJ/mol,respectively.Flow curves showed that the addition of Y element led to increase in peak stress and decrease in peak strain,and indicated that DRX started at lower strains in Mg-Zn-Y alloy than in Mg-Zn alloy.The stability domains of Mg-Zn-Y alloy were indicated in two domains as 1)300°C,0.001 s-1;350°C,0.01-0.1 s-1 and 400°C,0.01 s-1 and 2)450°C,0.01-0.1 s-1.Microstructural observations showed that DRX was the main restoration mechanism for alloys,and fully dynamic recrystallization of Mg-Zn-Y alloy was observed at 450°C.The instability domain in Mg-Zn-Y alloy was located significantly at high strain rates.In addition,the instability zone width of Mg-Zn and Mg-Zn-Y alloys increased with increasing strain,and cracks,twins and severe deformation were considered in these regions.
基金the Natural Sciences and Engineering Research Council of Canada (NSERC)Ontario Trillium Scholarships (OTS) program for providing financial support+8 种基金financial support by the Premier’s Research Excellence Award (PREA)Canada Foundation for Innovation (CFI)Ryerson Research Chair (RRC) programthe Ministry of Science and Technology of China (2014DFG52810)National Great Theoretic Research Project of China (2013CB632200)National Natural Science Foundation of China (Project 51474043)Ministry of Education of China (SRFDR 20130191110018)Chongqing Municipal Government(CSTC2013JCYJC60001)Chongqing Science and Technology Commission (CSTC2011gjhz50001)
文摘This study was aimed at identifying underlying strengthening mechanisms and predicting the yield strength of as-extruded Mg-Zn-Y alloys with varying amounts of yttrium （Y） element. The addition of Y resulted in the formation of ternary 1 （Mg3YZn6）, W （Mg3Y2Zn3） and LPSO （Mg12YZn） phases which subse- quently reinforced alloys ZM31 ＋ 0.3Y, ZM31 ＋ 3.2Y and ZM31 ＋ 6Y, where the value denoted the amount of Y element （in wt%）. Yield strength of the alloys was determined via uniaxial compression testing, and grain size and second-phase particles were characterized using OM and SEM. In-situ high-temperature XRD was performed to determine the coefficient of thermal expansion （CTE）, which was derived to be 1.38 x 10^-5 K^-1 and 2.35 x 10^-5 K^-1 for W and LPSO phases, respectively. The individual strengthening effects in each material were quantified for the first time, including grain refinement, Orowan looping, thermal mismatch, dislocation density, load-bearing, and particle shearing contributions. Grain refinement was one of the major strengthening mechanisms and it was present in all the alloys studied, irrespective of the second-phase particles. Orowan looping and crE mismatch were the predominant strengthening mechanisms in the ZM31＋0.3Y and ZM31 ＋ 3.2Y alloys containing I and W phases, respectively, while load-bearing and second-phase shearing were the salient mechanisms contributing largely to the superior yield strength of the LPSO-reinforced ZM31 ＋ 6Y alloy.2017 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science ＆ Technology.
基金financially supported by Beijing Municipal Science and Technology Commission(No.Z131100003213019)National Natural Science Foundation of China(Nos.51101002 and 51301006)Beijing Municipal Commission of Education(Nos.KM201310005001 and KM201110005001)
文摘The particles of Mg-Zn-Gd icosahedral quasicrystal master alloy were added into the AZ31 alloy by the repeated plastic working(RPW)process in order to improve the mechanical properties of the AZ31 alloy at room temperature.The microstructure and tensile properties of composites were investigated by scanning electron microscopy(SEM),transmission electron microscopy(TEM),X-ray diffraction(XRD),and tensile testing machine at room temperature.The results suggest that the RPW process can effectively refine the matrix and make the I-phase particles distribute uniformly.The ultimate tensile strength and the yield strength of the composites reach their maximum values of 362.3 and 330.5 MPa,respectively,when the amount of I-phase particles added is10 %.Meanwhile,the elongation of the composites decreases sharply.
基金supported financially by the Strategic New Industry Development Special Foundation of Shenzhen (No. JCYJ20170306141749970)the National Natural Science Foundation of China (Nos.51871211 and 51701129)+3 种基金the Natural Science Foundation of Guangdong Province (No.2018A030313950)the funds of International Joint Laboratory for Light Alloys,the National Key Research and Development Program of China (Nos. 2017YFB0702001 and 2016YFB0301105)Liaoning BaiQianWan Talents Programthe Innovation Fund of Institute of Metal Research (IMR),Chinese Academy of Sciences (CAS)
文摘Through investigating and comparing microstructure and crystallographic texture of as-extruded Mg-14Li and Mg-14Li-6Zn-1Y(in wt%)alloys,the differences in their mechanical anisotropy were investigated.It revealed that the formation of I-phase(Mg3Zn6Y,icosahedral structure)can effectively refine grain size.Moreover,compared with Mg-14Li alloy,the texture type of Mg-14Li-6Zn-1Y alloy changed slightly,but its texture intensity decreased remarkably.As a result,the stronger texture contributed to the"normal"mechanical anisotropy of Mg-14Li alloy with higher tensile strength and a lower elongation ratio along transverse direction(TD)than those along extrusion direction(ED).However,for Mg-14Li-6Zn-1Y alloy,the zonal distribution of I-phase particles along ED caused"abnormal"mechanical anisotropy,i.e.higher tensile strength and better plasticity along ED.
基金supported in part by grants from Chinese National Major Project for New Drug Innovation(2012ZX09303012-001)
文摘Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.
基金supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020,2009ZX09503-014,2012ZX09303012 and 2013ZX09402301)National Key Technology Support Program (2014BAI09B12)+1 种基金Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001)Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055)
文摘Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.
文摘The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials. Early clinical trials are no exception, with efforts to improve the eventual success rate of late stage trials through evolving phase I trial methodologies, the addition of extensive pharmacodynamic studies, and early adoption of patient selection strategies. Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges.
文摘Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.
文摘An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were distributed evenly, and the particle size ranged from 20 to 260 nm（ average size ： 67.5 nm ）. Soybean lecithin played an important role in the emulsion system due to its abilities of acting as both absorption enhancer for insulin uptake through sublingual mucosa and oily phase for the emulsion system. The laser confocal scanning microscopic（LCSM） study showed that FITC-labelled insulin could penetrate the sublingual mucosa of rabbits, and the phase diagrams of the emulsion system suggested that soybean lecithin could take the place of oily phase to construct a stable emulsion system even if the traditional oil was absent. The applications of soybean lecithin as pharmaceutical biomaterial were extended for the further usage by present studies.
文摘Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.
文摘Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.
文摘Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cytopathology of Nipple Aspirate Fluid (NAF) has been shown to be an important adjunct to the currently accepted standard of medical care, i.e. mammography, coupled with physical examination, for the diagnosis of breast cancer. This is especially important for the subset of women aged 18-50 who are not identified as “high risk”, and therefore, for whom mammography is not routinely recommended. The objective of this study was to determine if a new, patented Class II medical device, the Mammary Aspirate Specimen Cytology Test (MASCT) System, designed to collect NAF for subsequent cytological examination is safe and effective. Methods: The MASCT medical device is a modified breast pump and was used to obtain bilateral specimens from 34 healthy, non-pregnant, female subjects for cytopathological examination. A conventional breast disease work-up was performed (medical history/risk factor collection, clinical breast examination and mammogram) and NAF specimens collected. Specimen weight was measured and a cytopathological examination was performed. Vital signs measurements, clinical laboratory analysis, and adverse event reporting were performed. Results: Based on cytopathological evaluation and/or measurable weight changes on the specimen collection membrane filter, all breasts evaluated (100%) yielded nipple aspirate fluid. Specimen weights ranged from <1 to 37 mg and all specimens evaluated cytopathologically were deemed to be clinically useful. One patient’s specimen was not available for cytopathological examination due to specimen mishandling, resulting in 60 breasts (representing 30 subjects) being evaluated cytologically. Fifty-eight of sixty breasts evaluated cytopathologically (97%) were reported as cytology Class I, and 2 of 60 (3%) were reported as cytology Class IIa. Cytopathological findings correlated well with mammogram and clinical breast exam results. No adverse events, including pain from the collection procedure, were reported. Conclusion: Based on this clinical study, we conclude that the Mammary Aspiration Specimen Cytology Test device is safe and effective for the collection of mammary aspirate specimens for laboratory cytopatho-logical testing.
文摘The precondition of realizing feedback controlling DC DC converter to avoid chaotic state is to judge the behavior of the converter and take corresponding measures. In this paper, the output signals under different circuit parameters of the PWM buck converter have been analyzed. The method of using Fourier descriptor to extract output signals characteristics is put forward and proved to be a gist of identifying and classifying the behavior of DC DC converter. This method can establish a good foundation fo...
文摘The noncollinear optical parametric amplification in BBO crystal is theoretically investigated. The phase matching angle, gain bandwidth, optimal noncollinear angle and conversion efficiency for both type-I and type-II BBO are simulated. The numerical simulation results are important to the practical optical parametric amplification experiments with BBO crystal.
文摘Our aim in this paper is to study on the Caginalp for a conserved phase-field with a polynomial potentiel of order 2<em>p</em> - 1. In this part, one treats the conservative version of the problem of generalized phase field. We consider a regular potential, more precisely a polynomial term of the order 2<em>p</em> - 1 with edge conditions of Dirichlet type. Existence and uniqueness are analyzed. More precisely, we precisely, we prove the existence and uniqueness of solutions.
